JPH0321021B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing sulfones. More specifically, the present invention provides a compound having the general formula R ¹ -SO ₂ -R ² (1) [wherein R ¹ represents an aryl group or an alkyl group].
R ² is an alkyl group, an alkenyl group, an aralkyl group,
Indicates a cyanoalkyl group, haloalkyl group, or alkoxycarbonylalkyl group. ] This invention relates to a method for producing sulfones represented by the following. Sulfones represented by the above general formula (1) are important compounds as raw materials for producing various organic drugs. Conventionally, as a method for producing sulfones represented by the above general formula (1), for example, the method of Zwaneburg et al. [GEVeentra, B. Zwaneburg, Synthesis, 519
(1975)] is known. In this method, sodium sulfinate and tetrabutylammonium bromide are reacted to obtain tetrabutylammonium sulfinate, which is then reacted with an alkyl halide to produce the desired sulfones. However, this method requires complicated operations to synthesize tetrabutylammonium sulfinate, and moreover, it is essential to use twice the amount of sulfinic acid based on the amount of tetrabutylammonium bromide. Therefore, it is necessary to recover unreacted sodium sulfinate from the reaction mixture after the reaction is completed, but recovery of sodium sulfinate is difficult. Additionally, as an improvement to the above method, Maneskalki et al.'s method [F.
Manescalchi, M. Orena, D. Savoia, Synthesis,
445 (1979)] is known. This method uses Amberlyst A-26, an anion exchange resin, in place of tetrabutylammonium bromide. However, this method also requires complicated operations to synthesize sulfinic acid type Amberlyst A-26. As described above, none of the methods for producing sulfones known to date are satisfactory as industrial production methods. In view of the current situation, the present inventors have conducted extensive research to develop an industrial method for producing sulfones, and as a result,
The purpose of the present invention is achieved only when a sulfinate salt represented by the following general formula (2) and a halogen compound represented by the following general formula (3) are reacted in the presence of a compound represented by the following general formula (4). It was discovered that this purpose could be achieved. The present invention was completed based on this knowledge. That is, the present invention provides a compound having the general formula R ¹ SO ₂ M·nH ₂ O (2) [wherein R ¹ represents an aryl group or an alkyl group].
M represents an alkali metal atom. n is 0 or 1-4
indicates an integer. ] A sulfinate salt represented by ^the general formula R ² X represents a halogen atom. ] by reacting with a halogen compound represented by the general formula R ¹ -SO ₂ -R ² (1) [wherein R ¹ and R ² are the same as above. ] In producing sulfones represented by the following, the general formula R ³ O (C ₂ H ₄ O) _l (C ₃ H ₆ O) _n R ⁴ (4) [in the formula, R ³ and R ⁴ are the same or different and each represents a hydrogen atom, an alkyl group, an alkenyl group, an aryl group or an aralkyl group, l represents an integer of 4 or more, and m represents an integer of 0 or 1 or more. ] This relates to a method for producing sulfones, which is characterized by the presence of a compound represented by the following. According to the method of the present invention, it is completely unnecessary to use tetrabutylammonium sulfinate or sulfinate type Amberlyst A-26, which require complicated operations for synthesis, and therefore the workability is extremely good. The desired sulfones can be isolated from the reaction mixture with good purity and yield by simple operations such as distillation and recrystallization. Therefore, it can be said that the method of the present invention is an extremely suitable method for industrially producing sulfones. The sulfinate salts of general formula (2) used as starting materials in the present invention are all known compounds. In general formula (2), the aryl group represented by R ¹ is phenyl, 4-methylphenyl, 2,
Examples include 4-dimethylphenyl, 2,4,6-trimethylphenyl, p-methoxyphenyl, p-chlorophenyl, α-naphthyl, β-naphthyl, and examples of alkyl groups include methyl, ethyl, n-
Examples include propyl, isopropyl, n-butyl, isobutyl, and tert-butyl groups. Specific examples of the sulfinate of general formula (2) include sodium benzenesulfinate (potassium), sodium p-toluenesulfinate (potassium), sodium 2,4-dimethylbenzenesulfinate (potassium), 2, Sodium 4,6-trimethylbenzenesulfinate (potassium), p-methoxybenzenesulfinate sodium (potassium), p-
Sodium chlorobenzenesulfinate (potassium), sodium α-naphthalenesulfinate (potassium), sodium β-naphthalenesulfinate (potassium), sodium methanesulfinate (potassium), sodium ethanesulfinate (potassium), n-propane Examples include sodium (potassium) sulfinate, sodium (potassium) n-butanesulfinate, and hydrates thereof. The halogen compounds of general formula (3) used as the other starting material in the present invention are all known compounds. In general formula (3), the alkyl group represented by R ² is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,
Examples include tert-butyl, n-amyl, isoamyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-lauryl groups,
Examples of alkenyl groups include allyl, metaallyl, and crotyl groups; examples of aralkyl groups include benzyl, 2-phenylethyl, and 3-phenylpropyl; and examples of cyanoalkyl groups include cyanomethyl, 2-cyanoethyl, and 3-cyanoethyl. Examples of the haloalkyl group include propyl, -cyanobutyl, and chloromethyl, 2-chloroethyl, 3-chloropropyl, 4-chlorobutyl, bromomethyl, 2-bromoethyl, 3-bromopropyl, 4-bromobutyl, iodomethyl, and 2-iodoethyl. , 3-iodopropyl, 4-iodobutyl groups, etc. Examples of alkoxycarbonylalkyl groups include methoxycarbonylmethyl, methoxycarbonylethyl, methoxycarbonylpropyl, ethoxycarbonylmethyl, ethoxycarbonylethyl, ethoxycarbonylpropyl, propoxycarbonylmethyl, and polycarbonylmethyl. Examples include poxycarbonylethyl, propoxycarbonylpropyl, butoxycarbonylmethyl, butoxycarbonylethyl, butoxycarbonylpropyl groups, and the like. Examples of the halogen atom represented by X include chlorine atom, bromine atom, and iodine atom. Specific examples of the halogen compound of general formula (3) include methyl chloride, ethyl chloride, n-propyl chloride, isopropyl chloride, n-butyl chloride, n-amyl chloride, n-hexyl chloride, n-heptyl chloride, and n-chloride. Octyl, n-nonyl chloride, n-decyl chloride, n-chloride
- lauryl, allyl chloride, metaallyl chloride, crotyl chloride, benzyl chloride, -2-phenylethyl chloride, 3-phenylpropyl chloride, cyanomethyl chloride, -2-cyanoethyl chloride, -3-cyanopropyl chloride, -4-cyanobutyl chloride, Dichloromethane, 1,2-dichloroethane, 1,3-dichloropropane, 1,4-dichlorobutane, methoxycarbonylmethyl chloride, methoxycarbonylethyl chloride, methoxycarbonylpropyl chloride, ethoxycarbonylmethyl chloride, ethoxycarbonylethyl chloride, ethoxycarbonyl chloride Examples include propyl. In the present invention, the ratio of the sulfinate of general formula (2) to the halogen compound of general formula (3) is not particularly limited and can be appropriately selected from a wide range; Approximately equimolar ~
It is preferable to use 2 times the mole, preferably equimolar to 1.5 times the mole. In the present invention, it is essential that the compound represented by general formula (4) be present in the reaction system. In the general formula (4), the alkyl groups represented by R ³ and R ⁴ include methyl, ethyl, n-propyl, iso-propyl,
n-butyl, tert-butyl, n-amyl, iso-
amyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-lauryl,
n-cetyl, n-stearyl, etc., alkenyl groups include n-oleyl, aryl groups include phenyl, n-octylphenyl, n-nonylphenyl, naphthyl, etc., and aralkyl groups include benzyl, 2-phenylethyl, 3-phenylpropyl groups, etc. are included, respectively. Specifically, the compounds represented by the general formula (4) include polyethylene glycol-200, -300, -400, -600, -1000, -1500,
-1540, -2000, -4000, -6000, -20000, oxypropylene oxyethylene block copolymer -
2000, −3000, −4000, −8000, −10000 [Trademark: Emulgen PP series 150, 230, manufactured by Kao Atlas Co., Ltd.
250 and 290; New Paul manufactured by Sanyo Chemical Industries, Ltd.
pE series 61, 62, 64, 68, 74, 75, 78 and
88; Actinol p series manufactured by Matsumoto Yushi Pharmaceutical Co., Ltd.
1050, 2040, 2060, 2085 and 3035], mono or dimethyl ether, mono or diethyl ether, mono or dipropyl ether, mono or dibutyl ether, mono or dipentyl ether, mono or dihexyl ether, mono or diheptyl ether, mono or dioctyl ether, mono or dinonyl ether, mono or didecyl ether, monolauryl ether, monocetyl ether, monostearyl ether, monooleyl ether, monooctyl phenyl ether, monononyl phenyl ether, monophenyl ether, mononaphthyl Ether, monobenzyl ether, monophenyl ethyl ether, lauryl methyl ether, lauryl ethyl ether, lauryl propyl ether, lauryl butyl ether, cetyl methyl ether, cetyl ethyl ether, cetyl propyl ether, cetyl butyl ether, stearyl methyl ether, stearyl ethyl ether, stearyl Propyl ether, stearyl butyl ether, oleyl methyl ether, oleyl ethyl ether, oleyl propyl ether, oleyl butyl ether,
Octylphenyl methyl ether, octylphenyl ethyl ether, octylphenyl propyl ether, octylphenyl butyl ether, nonylphenyl methyl ether, nonylphenyl ethyl ether, nonylphenyl propyl ether, nonylphenyl butyl ether, diphenyl ether, dinaphthyl ether,
Examples include dibenzyl ether and diphenylethyl ether. Among these, polyethylene glycol (PEG)-400-dimethyl ether,
PEG-400-diethyl ether, PEG-400-di-n-propyl ether, PEG-400-di-n-
Butyl ether, PEG-600-dimethyl ether, PEG-600-diethyl ether, PEG-600
-di-n-propyl ether, PEG-600-di-
n-butyl ether, PEG-1000-dimethyl ether, PEG-1000-diethyl ether, PEG
-1000-di-n-butyl ether, PEG-400,
PEG-600 and PEG-1000 are particularly preferred. The amount of the compound of general formula (4) to be present in the reaction system is not particularly limited, but it is usually present at about 0.01 to 2 mol, preferably about 0.01 to 1 mol, per 1 mol of the sulfinate of general formula (2). Just let it happen. The reactions of the present invention are generally carried out in organic solvents. Examples of organic solvents include alcohols such as methanol, ethanol, propanol, and butanol, aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as tetrahydrofuran and dioxane, and ketones such as acetone and methyl ethyl ketone. can. Among these, alcohols are preferred. Further, in the present invention, the compound of the above general formula (4) can also be used as a solvent. The above reaction can be carried out either at room temperature or under heating, but is usually between room temperature and
The reaction proceeds suitably at around 70°C, preferably at room temperature to 60°C. The reaction time is generally about 1 to 9 hours. The target compound of the present invention thus produced can be easily isolated and purified from the reaction mixture by conventional separation means such as distillation, recrystallization, etc. Examples are given below. Example 1 9.8 g (0.05 mol) of sodium p-toluenesulfinate monohydrate, 10.3 g (0.075 mol) of butyl bromide, and 20 ml of PEG-400 were stirred at 60°C for 3 hours. After cooling, 200 ml of water was added to the reaction solution, and the mixture was extracted with benzene (20 ml x 3). The benzene layer was thoroughly washed with water and then dried, and the benzene was distilled off, followed by simple distillation under reduced pressure to obtain 9.5 g of n-butyl p-tolylsulfone (yield 90%). Example 2 Sodium p-toluenesulfinate monohydrate 9.8 g (0.05 mol), benzyl chloride 9.5 g (0.075 mol)
mol) and 40 ml of PEG-400 were stirred at 60°C for 2 hours. After cooling, the reaction solution was poured into 300ml of water.
The precipitated crystals were collected, washed with water, and recrystallized with ethanol to obtain 11.7 g of benzyl p-tolylsulfone (yield 94%). Examples 3 to 17 Using 0.05 mol of sodium p-toluenesulfinate monohydrate and 0.075 mol of the compound of general formula (3) listed in Table 1 below, react under the conditions listed in Table 1 below. Except for this, sulfones were obtained in the same manner as in Example 1 or 2.

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【table】

Claims (1)

[Claims] 1 General formula R ¹ SO ₂ M·nH ₂ O [In the formula, R ¹ represents an aryl group or an alkyl group.
M represents an alkali metal atom. n is 0 or 1-4
indicates an integer. ] A sulfinate salt ^represented by the general formula R ² X represents a halogen atom. ] by reacting with a halogen compound represented by the general formula R ¹ -SO ₂ -R ² [wherein R ¹ and R ² are the same as above. ] In producing sulfones represented by the following formula, the general formula R ³ O (C ₂ H ₄ O) _l (C ₃ H ₆ O) _n R ⁴ [in the formula, R ³ and R ⁴ are the same or They are different from each other and represent a hydrogen atom, an alkyl group, an alkenyl group, an aryl group or an aralkyl group, l represents an integer of 4 or more, and m represents an integer of 0 or 1 or more. ] A method for producing sulfones, characterized in that a compound represented by these is present.